Ion exchange (IEX) is a viable technology for the removal of natural organic matter (NOM) from surface water. One potential drawback of the IEX process, however, is the need for frequent regeneration of the resins using a brine solution which needs to be disposed of safely. Operating ion exchange systems in biological could potentially be a promising approach. By allowing a viable microbial community to grow on the resins, NOM removal could be achieved through biodegradation in addition to ion exchange. This process, here named biological ion exchange (BIEX), decreases the need for frequent regeneration and prolongs the life of the resins. The aim of this study was to further explore the efficacy of the BIEX process, operating in the long-term, at removing NOM and to investigate different mechanisms involved in the process. Two parallel and identical packed bed ion exchange columns were used in pilot scale, each column with a height of 1 m was halfway filled with ion exchange resin and operated with a filtration velocity of 1 m/h, without regeneration. Also, two parallel continuous stirred tank reactors, each with a volume of 400 mL, were operated in the lab scale, in biotic and abiotic conditions. The performance of the systems was assessed by monitoring the concentrations of dissolved organic carbon, different anions, and UV absorbance of water. In addition, several other parameters (i.e., THMFP, BDOC and ATP measurements, resin morphology) were monitored on a less frequent basis. Laboratory experiments involving biotic and abiotic conditions resulted in no significant difference in terms of performance and NOM removal. This was likely due to the type of reactor (i.e., stirred tank), as well as operating conditions that did not allow for sufficient growth of biofilm. Pilot experiment, on the other hand, had noticeable biological growth and demonstrated effective removal of NOM, after approximately 9 months. Extended NOM removal along with no chloride release after 60 days, positive ATP data through the bed, and significant sulphate release over the course of experiments, indicated that in addition to ion exchange, other mechanisms would be responsible for NOM removal.